Pancreatic exocrine carcinoma is currently the fourth most common cause of cancer deaths in the United States. Only 3% of patients with adenocarcinoma of the pancreas survive five years after diagnosis. Due to the lack of successful therapy, chemoprevention of pancreas may be one means of increasing survival in patients with pancreatic cancer. Monoterpenes have been shown to be efficacious in preventing mammary, liver, stomach, and lung cancers. A postulated mechanism that is of particular interest includes inhibition of isoprenylation of p21 ras. Both human and N-nitrosobis(2-oxopropyl)amine (BOP)-induced Syrian hamster pancreatic cancer have a high frequency of ras mutations (>90%). A question arises as to whether the more potent limonene analog, perillyl alcohol, could inhibit the formation of pancreatic carcinoma when administered throughout the initiation and promotion/progression stages of carcinogenesis. The goals of this proposal are to 1) Evaluate the chemopreventive effects of perillyl alcohol using the highly relevant animal model. 2) Evaluate whether perillyl alcohol will be more effective during the initiation or promotion/progression stages. 3) Evaluate whether perillyl alcohol will regress established pancreatic cancer in hamsters. 4) If chemoprevention is successful, evaluate whether inhibition of ras activation is involved. 5) Evaluate the progression of pancreatic cancer through the use of the hamster model by finding genetic changes such as mutations of p53 and p16 and overexpression of EGFR and the neu protein.